This project continues to focus upon leishmaniasis. The studies involve characterization of parasites recovered from patients, use of experimental models of leishmanial infection in genetic in-bred strains of mice, and examination of the immune response in humans with various clinical forms of leishmanial infections. In addition to the group of L. aethiopica isolates from recently studied cutaneous disease cases from Ethiopia, we have accumulated 6 further isolates from widely scattered regions of the world (Peru, Dominican Republic, Afghanistan and Morocco, which are in process of characterization. Some exceptions to the original general pattern of heat sensitivity of species has turned up; one member of the L mexicana complex and the L. aethiopica isolates were found to be sensitive to 35 degrees C. Our sequential studies of the histopathology of leishmanial lesions in the ears of BALB/c mice are continuing, and we have confirmed late metastatic spread of L. m. amazonensis in the resistant C3H mouse with a cloned isolate of the parasite. Work on the cell-mediated immune response in humans with leishmanial infection has comentrated mainly on assay of interleukin 2 (IL-2) and gamma interferon (gamma-INF) produced in lymphocyte cultures. We have also started to generate these lymphokines, along with lymphocyte blastogenesis to mitogens and antigens, using lymphocyte subsets --namely, unfractionated, total T cells and T 4 cells. A trial of gamma-INF therapy in two patients with diffuse cutaneous leishmaniasis is underway, but final results are not yet available.